Dr Markov CBIS Theory of ME/CFS - General Discussion

[Hip]

Viral infections were presumed, not causal, as soon as someone sees high titers to a virus they assume it is their cause, it has been like this for years within the ME/CFS community now, how many ME/CFS patients have been told it is Lyme disease.

In the case of enterovirus, it is not only chronically high antibody levels, but you also find this virus as a low-level infection if you perform PCR tests on tissue (not the blood), like on stomach biopsies, or muscle biopsies.

Many British studies found enterovirus in ME/CFS patient muscle tissues, and Dr John Chia found enterovirus in the stomach tissues. However, these tissue infections are also sometimes found in healthy controls, which suggests on their own, they may not trigger ME/CFS.



But there are theories like the immune priming theory of ME/CFS, which posit the immune system may be hyper-sensitized in ME/CFS, so that the immune response to a low-level enterovirus infection may be disproportionately high and exaggerated.

Interestingly, in studies on immune priming, when immune cells are pre-exposed to LPS, they can subsequently become hyper-sensitized and mount exaggerated responses.

So LPS leaking into the bloodstream from a low-level kidney infection (or perhaps from leaky gut), might hyper-sensitize the immune system, so that later when a virus comes along, the immune response to even a low-level viral infection is very large, leading to ME/CFS symptoms.


A Simon McGrath Phoenix Rising article on the immune priming theory of ME/CFS is found here. I wrote this post on immune priming.

 

[Aidan Walsh]

In the case of enterovirus, it is not only chronically high antibody levels, but you also find this virus as a low-level infection if you perform PCR tests on tissue (not the blood), like on stomach biopsies, or muscle biopsies.

Many British studies found enterovirus in ME/CFS patient muscle tissues, and Dr John Chia found enterovirus in the stomach tissues. However, these tissue infections are also sometimes found in healthy controls, which suggests on their own, they may not trigger ME/CFS.



But there are theories like the immune priming theory of ME/CFS, which posit the immune system may be hyper-sensitized in ME/CFS, so that the immune response to a low-level enterovirus infection may be disproportionately high and exaggerated.

Interestingly, in studies on immune priming, when immune cells are pre-exposed to LPS, they can subsequently become hyper-sensitized and mount exaggerated responses.

So LPS leaking into the bloodstream from a low-level kidney infection (or perhaps from leaky gut), might hyper-sensitize the immune system, so that later when a virus comes along, the immune response to even a low-level viral infection is very large, leading to ME/CFS symptoms.


A Simon McGrath Phoenix Rising article on the immune priming theory of ME/CFS is found here. I wrote this post on immune priming.

I was looking at one of the links you mentioned above & saw Parkinson's & I recall Dr. Ian Carroll at Stanford pain clinic found spontaneous spinal fluid leaks even in Parkinson's, Marfan's, ME/CFS, EDS Hypermobility.

He first got involved with this, his daughter who is Autistic she was given an LP she became totally
bedbound, they later found out she was leaking from the site of the LP...I have seen countless go decades to
find out they are leaking spinal fluids,

I have even seen some diagnosed with Genetic (HFI) born with hereditary fructose intolerance, one Woman told me she waited 28 years of chronic illness to be diagnosed properly. Even (HATS) Hereditary Alpha Tryptasemia Syndrome multiple copies of the tryptase gene is another test that needs to be done or even (GSD) Glycogen Storage Disease types.

Stiff Person Syndrome 'Tin Man illness' is another set of test exclusions...

 

[Hip]

What is LP?

@Aidan Walsh, you might like to format your posts into paragraphs of say 2 to 4 lines. Lots of ME/CFS patients have neurological problems that make it hard for them to read text unless it is formatted into paragraphs.

 

[Aidan Walsh]

What is LP?

@Aidan Walsh, you might like to format your posts into paragraphs of say 2 to 4 lines. Lots of ME/CFS patients have neurological problems that make it hard for them to read text unless it is formatted into paragraphs.

thanks, I tried to fix it up but most of the time it goes back to the same format, so I used 2 lines spaces

 

[Pyrrhus]

What is LP?

Lumbar puncture, AKA spinal tap

 

[Hip]

thanks, I tried to fix it up but most of the time it goes back to the same format, so I used 2 lines spaces

What throws me is the text that is split mid-sentence by a new line.

 

[Aidan Walsh]

What throws me is the text that is split mid-sentence by a new line.

Must be my brain as well

 

[bensmith]

He is saying he doesnt think bed ridden parents can be helded? I guess they don’t treat server then?

 

[EddieB]

I think Dr Jay Goldstein's ME/CFS treatments were often flash-in-the-pan short-lived gimmicky effects he obtained from various drugs, rather than any long-lasting solutions to treating ME/CFS.

I actually had an amazing 2-week near remission from one of Goldstein's drugs: the antidepressant Wellbutrin (bupropion). I thought I had found my personal escape from ME/CFS. But then exactly two weeks later, the drug just stopped working for me, and has never worked since.

I had a near identical experience with Mirtazapine/ remeron. Mine lasted around 90 days. The startup brought a severe increase in all symptoms, then a moderate improvement. Then suddenly all went bad, and the withdrawal was horrible. Still haven’t recovered to prior.

I suspect one of two things happened,
1. These drugs can act as immune stimulants
2. These drugs can alter gut microbes

 

[Hip]

On the Russian language ME/CFS forum www.forums.epstein-barr-virus.ru, there is a thread about Dr Igor Markov. You can use Google Translate to read this thread (or better still is the Chrome browser with Google translation built in).

There is an interesting comment about Dr Markov curing chronic sinusitis, but I could not find any stories anywhere on this Russian forum about Dr Markov curing ME/CFS. Nor could I find any talk about autovaccines.


Regarding sinusitis, one member of that forum said:

I at one time (in 2013) cured chronic sinusitis with this doctor (I suffered for 16 years, after acute sinusitis and "puncture" in the hospital - there were constant relapses 2-3 times a year after each ARVI or at sea - I regularly treated with antibiotics when it was completely unbearable, or sometimes all sorts of cuckoos helped).

The cause of this sinusitis was Staphylococcus aureus and Klebsiella penvmonia, during this time they became insensitive to many antibiotics and reached the point that in 2012 I had sinusitis 7-8 times a year.

I find this interesting, as it does tend to support Dr Markov's view that antibiotics may fail to bring bacterial infections on the mucous membranes fully under control (in this case the mucous membranes of the sinuses), whereas autovaccines are able to achieve this.

Obviously it is never possible to fully eradicate a bacterium from the body, as bacteria have many ways of avoiding being totally eliminated. Antibiotics can address a current flare up of an infection, but they cannot eliminate the bacteria, so once you stop the antibiotics, there is the potential for the infection to flare up again.

Autovaccines also cannot eliminate the bacteria; but because they train the immune system to better fight the infection, and because that training will be remembered by the immune system, it may be that autovaccines provide better long-term protection against bacterial infection flare up than antibiotics.

 

[andyguitar]

Why won't you do a clinical trial.

The cost would be very high.

 

[andyguitar]

it may be that autovaccines provide better long-term protection against bacterial infection flare up than antibiotics.

Or it may be that the autovaccines are modulating the immune system. So it's more a case of the patients immune system over reacting to a pathogen that for most would not cause any symptoms and the long course of vaccines damps down that over reaction. Seems odd to me that if a vaccine can stimulate the immune system to attack a bacteria why would it need to be given so many time over such a long time frame?

 

[Alvin2]

Why won't you do a clinical trial. Please tell me!

You know why.

Anyone who actually comes up with a miracle cure would love to have it validated and accepted by the scientific community.
Imagine the fame and dollars that would roll in. Not to mention recognition, cure a major disease that has no treatment and one would be a contender for a Nobel prize. Just imagine someone discovered a game changing treatment for Cancer, Parkinsons, MS, Alzheimers...

The reason these miracle cures toil in obscurity is that the bright light of scrutiny would crush their grandiose claims and they know it. They cite anecdotal evidence, data that only they have access to and refuse to release, and make grandiose proclamations. And of course conspiracy theories, big pharma is out to get them, the government is suppressing their cures and so forth. So that they never have to put up real evidence. If they have come up with something it would go viral (no pun intended) and everyone would be chasing it and being cured.

 

[Hip]

So it's more a case of the patients immune system over reacting to a pathogen that for most would not cause any symptoms and the long course of vaccines damps down that over reaction. Seems odd to me that if a vaccine can stimulate the immune system to attack a bacteria why would it need to be given so many time over such a long time frame?

In Dr Markov's theory, it is the endotoxin (LPS) released into the bloodstream by a bacterial infection in the kidney that plays a causal role in ME/CFS.

So the idea of the autovaccine is to stimulate the immune response against these bacteria, in order to reduce the levels of these bacteria, which in turn should reduce the amount of LPS entering the blood.

I think the immune stimulation of a vaccine will wear off over time, so that may be why it sometimes requires repeat courses of autovaccine.

In Prof Gottfries's Staphylococcus toxoid vaccine treatment of ME/CFS, repeat vaccination every month was required in order to keep ME/CFS at bay.



All gram negative bacteria produce LPS (LPS is a toxin found in the cell wall of gram negative bacteria). Wikipedia says gram negative bacteria include:

• Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens (these are often found in the urinary tract)
• Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa (often found in respiratory tract)

Gram positive bacteria do not produce LPS. Gram positive bacteria include Staphylococcus, Streptococcus and Enterococcus.

However, both gram positive and gram negative bacteria can release exotoxins; the alpha toxin released by Staphylococcus aureus is one example.

 

[Martin aka paused||M.E.]

Martin aka paused//M.E., at 6:41 PM, June 12:
- Chronic Bacterial Intoxication Syndrome© (CBIS) and Nephrodysbacteriosis© - copyright non-property personal right to title of the diseases.

- 12-years (2009-2021) systematic scientific examination/observation of abt.4500 patients w/ symptomes of ME/CFS, 4288 patients treated, 3975 of them with full convalescence during the follow-up observation,
strict clinical, bacteriological & toxicological examinations, developed differential diagnostics of ME/CFS-CBIS, abt. 150 pages of scientific reports on ME/CFS-CBIS etc. etc.
Is this not serious studies ?!

- Many clinical (more than 70) symptomes of ME/CFS-CBIS, diagnosed usually (before us) as different diseases – yes, but they really have one focus of chronic bacterial infections in the kidneys, to be treated by one therapeutic means – by autovaccines.

And else: we do not try to convince all ME/CFS-patients to follow our findings ME/CFS-CBIS and recommendations on treatment, simply we give the opportunity to those who want, being right diagnosed and treated, to return to a normal life.

No a study is something completely different. Your report is clinical practice. You don't give replicable data. You only offer to be treated BY YOU. This is not about science.

And you don't understand what a copyright is.

I'm out of this thread. Thank you!

 

[Hip]

A well-written and pertinent paper for this discussion:

The Endotoxin Hypothesis of Neurodegeneration


Some excerpts from this paper:

The endotoxin hypothesis of neurodegeneration is the hypothesis that endotoxin causes or contributes to neurodegeneration.

Endotoxin is a lipopolysaccharide (LPS), constituting much of the outer membrane of gram-negative bacteria, present at high concentrations in gut, gums and skin and in other tissue during bacterial infection.

Blood plasma levels of endotoxin are normally low, but are elevated during infections, gut inflammation, gum disease and neurodegenerative disease.

Adding endotoxin at such levels to blood of healthy humans induces systemic inflammation and brain microglial activation.

Adding high levels of endotoxin to the blood or body of rodents induces microglial activation, priming and/or tolerance, memory deficits and loss of brain synapses and neurons.

The endotoxin hypothesis is unproven, but if correct, then neurodegeneration may be reduced by decreasing endotoxin levels or endotoxin-induced neuroinflammation.

LPS link to Alzheimer's:

Endotoxin promotes amyloid β and tau aggregation and neuropathology, suggesting the possibility that endotoxin synergises with different aggregable proteins to give different neurodegenerative diseases.

Blood and brain endotoxin levels are elevated in Alzheimer’s disease, which is accelerated by systemic infections, including gum disease.

LPS link to Parkinson's:

Intestinal permeability increases early in Parkinson’s disease, and injection of endotoxin into mice induces α-synuclein production and aggregation, as well as loss of dopaminergic neurons in the substantia nigra.

LPS and TLR4:

Endotoxin causes inflammatory activation mainly via activating TLR4

Note: in the low-dose naltrexone (LDN) treatment of ME/CFS and other diseases, the ability of naltrexone to block TLR4 on microglia is one theory as to why LDN works.



LPS and caspase-1:

Intracellular LPS can also directly activate murine caspase-11 (caspase-4 or caspase-5 in humans), which may then cleave and activate caspase-1

It's interesting that LPS can activate caspase-1, because a paper I looked at recently suggests caspase-1 is critical for coxsackievirus B replication. So in this way, LPS leaking into the bloodstream might be promoting coxsackievirus B infection in ME/CFS patients. Which might explain why ME/CFS patients have trouble fully clearing coxsackievirus B.



Some background on LPS endotoxin:

Endotoxin was originally called ‘endotoxin’, because it was a toxin within the bacteria, to distinguish it from ‘exotoxins’ that were released from bacteria.

However, we now know that (i) endotoxin is released by bacteria and (ii) the toxicity of endotoxin is due to the host’s inflammatory over-reaction to it, rather than an intrinsic toxicity to animal cells

LPS constitutes much of the surface of gram-negative bacteria, and thus, animals selected by bacterial diseases have evolved innate immune receptors to detect it with high sensitivity, inducing a strong innate (and adaptive) immune response.

This response protects against gram-negative bacterial disease, by promoting the clearance of the bacteria, removing the source of endotoxin.

However, (i) if endotoxin levels are too high, they cause acute death by septic shock, and (ii) if endotoxin is not cleared from the blood, it can promote a chronic inflammatory state, which may contribute to multiple chronic diseases

Where does LPS in the blood come from?

Active bacterial infections may produce endotoxin, and for example, urinary tract infections are associated with dementia, delirium and other neuropsychiatric disorders.

However, in the absence of infection, endotoxin still crosses the mucosal membranes of gut, gums, nose or lungs, the main source being intestinal permeability.

Can LPS in the blood cause disease?

Does endotoxin in blood cause neurodegeneration? It is not ethical to test this directly in humans, but this question has been tested in animals.

In rodents, a single intraperitoneal injection of 5 mg LPS/kg causes acute microglial activation in the brains that persists for at least 12 months, and results in loss of dopaminergic neurons in the substantia nigra 10 months later.

Multiple doses of 1 mg LPS/kg (over several days), or chronic endotoxin, cause more rapid neurodegeneration and have been used as models of Parkinson’s or Alzheimer’s disease.

How does LPS endotoxin in the blood get into the brain:

It is not entirely clear how peripheral endotoxin enters the brain. Endotoxin is found in rat brain in physiological conditions and might cross the blood-brain barrier bound to lipoproteins via lipoprotein transport mechanisms.

LPS endotoxin in the blood can trigger immune priming in the brain (thus underpinning the immune priming theory of ME/CFS mentioned earlier):

Blood endotoxin may ‘prime’ microglia to neurodegenerative stimuli (such as amyloid β, tau or α-synuclein), or alternatively, neurodegenerative stimuli (such as aggregating amyloid β, tau or α-synuclein) may prime microglia to endotoxin challenge—either way they synergise to induce neurodegeneration.

LPS in the blood might also weaken immunity by causing immune tolerance:

Conversely, blood endotoxin may induce tolerance and decrease activation of microglia, which may reduce brain protective functions such as phagocytosis of protein aggregate or debris.

The paper's conclusions and general ideas on treatment options to reduce blood LPS levels:

Increased endotoxin is associated with neurodegenerative disease, and increased endotoxin can cause neurodegeneration, but whether neurodegenerative disease is caused by increased endotoxin is not known.

Testing this causal link depends on determining whether reducing endotoxin levels or endotoxin actions reduces neurodegenerative disease pathology. Possible means to do this and therefore potential treatment targets include:

• (i) changing the gut microbiome to species with less or less-toxic LPS
• (ii) reducing intestinal permeability
• (iii) reducing peripheral, peridonatal and/or brain infections
• (iv) reducing blood endotoxin levels
• (v) reducing LPS actions on, or permeability across, the blood-brain barrier
• (vi) inhibiting TLR4 or other LPS receptors
• (vii) inhibiting endotoxin-induced microglial activation and neurotoxicity

 

[Hip]

Just discovered a possible connection between Dr Markov's kidney infection theory of ME/CFS that is detailed in this thread (where LPS and exotoxins leak into the bloodstream, causing ME/CFS according to his theory), and Dr Robert Phair's interest in the mutations of the IDO2 gene found in ME/CFS patients. @HTester

As I understand it, the mutations in the IDO2 gene often found in ME/CFS patients reduce the effectiveness of the IDO2 enzyme.

Well, this study found that IDO2 knock-out mice had increased production of inflammatory cytokines when exposed to LPS.

So this suggests people who have IDO2 mutations which reduce the effectiveness of IDO2 will be more susceptible to the pro-inflammatory effects of LPS in the bloodstream.

 

[Hip]

When quoting another member's post, this very short video shows you how to select the appropriate paragraphs from their post to quote.

 

[Alvin2]

A well-written and pertinent paper for this discussion:

The Endotoxin Hypothesis of Neurodegeneration


Some excerpts from this paper:

If its part of ME they should detectable and OMF or other researchers should be able to find them.

 

[max_yazhbin]

I am glad I am not the only one whose bullshit filter went ballistic on this one.